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1.
  • Hilke, Susanne, et al. (författare)
  • Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation : possibly a nongenomic/indirect effect
  • 2005
  • Ingår i: European Journal of Neuroscience. - 0953-816X. ; 21:8, s. 2089-2099
  • Tidskriftsartikel (refereegranskat)abstract
    • Administration of 17β-estradiol to ovariectomized rats increased the concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in the same brain region in the proestrous phase of a normal estrous cycle. Tamoxifen® did not block the 17β-estradiol-induced increase in the concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a decrease of extracellular galanin-LI (P < 0.001) 1−2 h after treatment with 17β-estradiol, indicating a decreased release of galanin. For comparision, we studied the concentrations of neuropeptide Y, which were not influenced significantly in any of the regions studied. Taken together our results suggest that 17β-estradiol inhibits galanin release, presumably from noradrenergic nerve terminals, and primarily via a nongenomic/indirect action, not necessarily involving the classical nuclear receptors ER-α or ER-β. These rapid estrogen-induced changes in galanin release could influence transmitter signalling and plasticity in the hippocampal formation.
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2.
  • Hilke, Susanne, et al. (författare)
  • Galanin in the hippocampal formation of female rats : effects of 17beta estradiol
  • 2005
  • Ingår i: Neuropeptides. - 0143-4179. ; 39:3, s. 253-257
  • Tidskriftsartikel (refereegranskat)abstract
    • 17β-Estradiol induced an increase in tissue concentrations of galanin in the hippocampal formation of ovariectomized rats. This increase was dose- and time dependent, and occurred already 60 min after steroid administration and was not blocked by Tamoxifen®. There was also an increase in galanin in the pro-estrous phase in regularly cycling rats. The estrogen-induced rapid increase may at least in part be due to decreased release of galanin as demonstrated by in vivo microdialysis studies. Thus, sex steroid hormones may influence signalling molecules in brain areas of importance for cognitive functions.
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3.
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4.
  • Holm, Lovisa, et al. (författare)
  • Changes in galanin and GalR1 gene expression in discrete brain regions after transient occlusion of the middle cerebral artery in female rats
  • 2012
  • Ingår i: Neuropeptides. - Elsevier. - 0143-4179. ; 46:1, s. 19-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Injury to neurons results in upregulation of galanin in some central and peripheral systems, and it has been suggested that this neuropeptide may play a protective and trophic role, primarily mediated by galanin receptor 2 (GalR2). The objective of the present study was to investigate galanin, GalR1, GalR2 and GalR3 gene expression in the female rat brain seven days after a 60-min unilateral occlusion of the middle cerebral artery followed by reperfusion. Quantitative real-time PCR was employed in punch-biopsies from the locus coeruleus, somatosensory cortex and dorsal hippocampal formation including sham-operated rats as controls. Galanin gene expression showed a ~2.5-fold increase and GalR1 a ~1.5-fold increase in the locus coeruleus of the ischemic hemisphere compared to the control side. Furthermore, the GalR1 mRNA levels decreased by 35% in the cortex of the ischemic hemisphere. The present results indicate that a stroke-induced forebrain lesion upregulates synthesis of galanin and GalR1 in the locus coeruleus, a noradrenergic cell group projecting to many forebrain areas, including cortex and the hippocampal formation. These results support the notion that galanin may play a role in the response of the central nervous system to injury and have trophic eff ects.
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5.
  • Holm, Lovisa, et al. (författare)
  • Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats
  • 2011
  • Ingår i: Neuropeptides. - Elsevier Science B.V., Amsterdam. - 0143-4179. ; 45:1, s. 17-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have shown that injury to the central and peripheral nervous system can increase expression of galanin, a 29 amino acid neuropeptide. Moreover, there is evidence that galanin, especially through its galanin receptor 2 (GalR2) receptor, plays a neuroprotective role in different injury models. However, direct studies of a possible neuroprotective effect of galanin in experimental stroke models are lacking. Galanin, a GalR2/3 agonist or artificial CSF was continuously infused intracerebroventricularly (i.c.v.) in naive female rats after a 60 min transient and focal occlusion of the middle cerebral artery. The animals were sacrificed, and the ischemic lesion was visualized using 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The lesion was 98% larger after i.c.v, administration of the GalR2/3 agonist (2.4 nmol/day) seven days after occlusion compared to artificial CSF (p = 0.023). No statistically significant differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24 nmol/day; p = 0.939, 0.715 and 0.977, respectively). There was no difference in the size of the ischemic lesions measured after three days in the galanin-treated group (2.4 nmol/d) compared to artificial CSF (p = 0.925). The present results show, surprisingly, that a GalR2/3 agonist doubled the size of the ischemic lesion. Whether this effect primarily reflects the properties of the current model, species, gender and/or the mode of galanin administration, e.g. causing desensitization, or whether galanin indeed lacks neuroprotective effect of its own, remains to be corroborated.
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6.
  • Ingberg, Edvin, et al. (författare)
  • Methods for long-term 17 beta-estradiol administration to mice
  • 2012
  • Ingår i: General and Comparative Endocrinology. - Elsevier. - 0016-6480. ; 175:1, s. 188-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17 beta-estradiol. However, a thorough assessment of the methods for long-term administration of 17 beta-estradiol to mice is lacking. The fact that 17 beta-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17 beta-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 mu g 17 beta-estradiol/mL sesame oil), or a novel peroral method (56 mu g 17 beta-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17 beta-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within - except on one occasion - the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17 beta-estradiol, superior to the widely used commercial pellets.
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7.
  • Isaksson, Ida-Maria, et al. (författare)
  • Methods for 17 beta-oestradiol administration to rats
  • 2011
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Informa Healthcare. - 0036-5513. ; 71:7, s. 583-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that the beneficial or harmful effects of oestrogens in stroke are dose-dependent. Rats are amongst the most frequently used animals in these studies, which calls for thoroughly validated methods for administering 17 beta-oestradiol to rats. In an earlier study we characterised three different administration methods for 17 beta-oestradiol over 42 days. The present study assesses the concentrations in a short time perspective, with the addition of a novel peroral method. Female Sprague-Dawley rats were ovariectomised and administered 17 beta-oestradiol by subcutaneous injections, silastic capsules, pellets and orally (in the nut-cream Nutella (R)), respectively. One group received 17 beta-oestradiol by silastic capsules without previous washout time. Blood samples were obtained after 30 minutes, 1, 2, 4, 8, 12, 24, 48 and 168 hours and serum 17 beta-oestradiol (and oestrone sulphate in some samples) was subsequently analysed. For long-term characterisation, one group treated perorally was blood sampled after 2, 7, 14, 21, 28, 35 and 42 days. At sacrifice, uterine horns were weighed and subcutaneous tissue samples were taken for histological assessment. The pellets, silastic capsule and injection groups produced serum 17 beta-oestradiol concentrations that were initially several orders of magnitude higher than physiological levels, while the peroral groups had 17 beta-oestradiol levels that were within the physiological range during the entire experiment. The peroral method is a promising option for administering 17 beta-oestradiol if physiological levels or similarity to womens oral hormone therapy are desired. Uterine weights were found to be a very crude measure of oestrogen exposure.
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8.
  • Isaksson, Ida-Maria, et al. (författare)
  • Methods for 17β-oestradiol administration to rats
  • 2011
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - Informa Healthcare. - 0036-5513. ; 71:7, s. 583-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that the beneficial or harmful effects of oestrogens in stroke are dose-dependent. Rats are amongst the most frequently used animals in these studies, which calls for thoroughly validated methods for administering 17β-oestradiol to rats. In an earlier study we characterised three different administration methods for 17β-oestradiol over 42 days. The present study assesses the concentrations in a short time perspective, with the addition of a novel peroral method. Female Sprague-Dawley rats were ovariectomised and administered 17β-oestradiol by subcutaneous injections, silastic capsules, pellets and orally (in the nut-cream Nutella®), respectively. One group received 17β-oestradiol by silastic capsules without previous washout time. Blood samples were obtained after 30 minutes, 1, 2, 4, 8, 12, 24, 48 and 168 hours and serum 17β-oestradiol (and oestrone sulphate in some samples) was subsequently analysed. For long-term characterisation, one group treated perorally was blood sampled after 2, 7, 14, 21, 28, 35 and 42 days. At sacrifice, uterine horns were weighed and subcutaneous tissue samples were taken for histological assessment. The pellets, silastic capsule and injection groups produced serum 17β-oestradiol concentrations that were initially several orders of magnitude higher than physiological levels, while the peroral groups had 17β-oestradiol levels that were within the physiological range during the entire experiment. The peroral method is a promising option for administering 17β-oestradiol if physiological levels or similarity to women's oral hormone therapy are desired. Uterine weights were found to be a very crude measure of oestrogen exposure.
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9.
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10.
  • Rugarn, Olof, et al. (författare)
  • Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain
  • 1999
  • Ingår i: Peptides. - 0196-9781. ; 20:6, s. 743-748
  • Tidskriftsartikel (refereegranskat)abstract
    • Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.
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